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Study Ties IVF To Rare Birth Defect

Leading researcher finds no cause for concern

FRIDAY, Nov. 22, 2002 (HealthDayNews) -- In vitro fertilization (IVF) procedures may be associated with a rare birth defect syndrome that predisposes children to certain cancers, scientists say.

However, an IVF pioneer says the study is small, the association is not proven, and there is absolutely no cause for concern until much more research is done.

The study authors agree that the findings need to be validated and the association needs to be confirmed by looking at larger numbers of people.

The research is "not trying to raise a red flag," says Dr. Andrew Feinberg, a professor of medicine at Johns Hopkins and co-author of the study, published online now and in the January 2003 issue of the American Journal of Human Genetics. However, the issue, he says, "deserves study."

Feinberg and his co-author, Dr. Michael DeBaun of Washington University School of Medicine in St. Louis, looked at data from a national registry of patients with Beckwith-Wiedemann syndrome (BWS), a rare condition marked by excessive growth of various tissues in the body. The registry was set up in 1994.

They found that IVF-initiated conception was six times more common in the registry than in the general population.

In all, they found seven infants in the registry of 344 who had been conceived via IVF. At least five had been conceived with a procedure called intracytoplasmic sperm injection, in which a single sperm is injected into a mature egg to overcome male fertility problems.

BWS affects about one of every 15,000 newborns, occurring when genes are abnormally altered. The alternations are not to the DNA sequence itself, Feinberg says, but are so-called "epigenetic" changes, ones that modify the gene in some way other than changing the DNA sequence.

Children born with BWS may have an enlarged tongue, defects in the abdominal wall, weigh more than most children, have earlobe creases or pits behind the upper ear, and other characteristics. Experts say the condition may predispose children to a malignant kidney condition called Wilms tumor, neuroblastoma (a malignant tumor in the autonomic nervous system or in the adrenal gland), and other cancers.

The study originated by chance, Feinberg says. "Mike [DeBaun, his co-author] had noticed there were a fair number of patients who had been born via IVF. So, two years ago we decided to add to the questionnaire and ask, 'Did you have assisted reproductive technology?'"

Exactly how IVF and the syndrome might be associated is not known, Feinberg says. It might be some aspect of the culture during the procedure or the method of combining the sperm and the egg.

Feinberg emphasizes that the finding should not cause concern for those who have used IVF or most who are considering it. "If someone has a family history of BWS, they should probably talk to a genetic counselor," he says.

An IVF pioneer says there is absolutely no cause for concern. "The problem with this report is that it's not really a formal study looking at Beckwith-Wiedemann syndrome and IVF," says Dr. Richard P. Marrs, director of the Center for Reproductive Medicine at Santa Monica-UCLA Medical Center. "Basically, what they've got are seven kids born via IVF with BWS out of 344 in the registry."

That's a small number, he notes, considering the number of children born via IVF annually, and it's not certain that the IVF had an impact on the development of the disorder. More than 30,000 births in the United States were IVF-assisted in 1999, the latest year for which figures are available from the U.S. Centers for Disease Control and Prevention.

Feinberg counters that it was a formal study, that they systematically assessed the method of conception and found that the prevalence of assisted reproduction births in the registry was six times the number of assisted reproduction births in the United States as a whole.

Overall, Marrs says, research has shown the incidence of abnormalities in IVF babies is actually lower than in natural birth babies year to year. That's partly due, he says, to the selection process in IVF, in which the healthiest embryos are selected.

"What they need to do, if they are saying this syndrome is related to IVF -- which it could be, but we don't know -- is to look at 30, 40, 50 thousand IVF births." That would give a more accurate picture, Marrs says, and help the scientists determine if there is a true cause-and-effect relationship.

Feinberg says they want to look at bigger numbers, too, and hope to work with the IVF community to research the association they found more intently.

What To Do

For more information on infertility, go to the American Society for Reproductive Medicine. For information on Beckwith-Wiedemann syndrome, visit the Beckwith-Wiedemann Support Network.

SOURCES: Andrew Feinberg, M.D., professor, medicine, Johns Hopkins School of Medicine, Baltimore; Richard P. Marrs, M.D., director, Center for Reproductive Medicine, Santa Monica-UCLA Medical Center, Santa Monica, Calif.; January 2003 American Journal of Human Genetics
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